MOSPD2 is an endoplasmic reticulum–lipid droplet tether functioning in LD homeostasis

Mehdi Zouiouich (1) , Thomas Di Mattia (1) , Arthur Martinet (1) , Julie Eichler (1) , Corinne Wendling (1) , Nario Tomishige (2) , Erwan Grandgirard (1) , Nicolas Fuggetta (3) , Catherine Fromental-Ramain (1) , Giulia Mizzon (4) , Calvin Dumesnil (5) , Maxime Carpentier (5) , Bernardo Reina-San-Martin (1) , Carole Mathelin (1) , Yannick Schwab (4) , Abdou Rachid Thiam (5) , Toshihide Kobayashi (2) , Guillaume Drin (3) , Catherine Tomasetto (1) , Fabien Alpy (1)

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
2 LBP - Laboratoire de Bioimagerie et Pathologies
3 IPMC - Institut de pharmacologie moléculaire et cellulaire
4 EMBL - European Molecular Biology Laboratory [Heidelberg]
5 LPTENS - Laboratoire de Physique Théorique de l'ENS [École Normale Supérieure]

Membrane contact sites between organelles are organized by protein bridges. Among the components of these contacts, the VAP family comprises ER–anchored proteins, such as MOSPD2, that function as major ER–organelle tethers. MOSPD2 distinguishes itself from the other members of the VAP family by the presence of a CRAL-TRIO domain. In this study, we show that MOSPD2 forms ER–lipid droplet (LD) contacts, thanks to its CRAL-TRIO domain. MOSPD2 ensures the attachment of the ER to LDs through a direct protein–membrane interaction. The attachment mechanism involves an amphipathic helix that has an affinity for lipid packing defects present at the surface of LDs. Remarkably, the absence of MOSPD2 markedly disturbs the assembly of lipid droplets. These data show that MOSPD2, in addition to being a general ER receptor for inter-organelle contacts, possesses an additional tethering activity and is specifically implicated in the biology of LDs via its CRAL-TRIO domain.

Domaines: Biologie cellulaire

Mehdi Zouiouich, Thomas Di Mattia, Arthur Martinet, Julie Eichler, Corinne Wendling, et al.. MOSPD2 is an endoplasmic reticulum–lipid droplet tether functioning in LD homeostasis. Journal of Cell Biology, 2022, 221 (6), ⟨10.1083/jcb.202110044⟩. ⟨hal-03652373⟩